# T-CELLS AND DISEASES

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 1993 · $216,487

## Abstract

Rheumatoid arthritis (RA) is a heterogenous disease characterized by
chronic polyarthritis in genetically predisposed individuals. A number of
lines of evidence suggest that T cells may play an important role in RA.
Our preliminary data reveal that 20% of RA patients have markedly expanded
V-alpha12 bearing CD8+ T cells in their peripheral blood. These T cells
have undergone clonal expansion based on the analysis of their V-alpha and
V-beta sequences and have a conserved J-alpha motif in their junctional
region. These cells carry the previously activated (CD45RO) phenotype and
express markers of ongoing or chronic activation (MHC class II+ and VLA-
1+).  The patients with expanded V-alpha12+ T cell populations have an
increased frequency of the HLA-DQ2 allele. These features of the sequence
analysis, including use of a single V-alpha (V-alpha12) and the presence
of a J-alpha motif are consistent with an antigen driven expansion. The
HLA-DQ2 association raises the possibility that this MHC molecule is
involved in antigen presentation to the expanded T cells.

We propose to study the specificity and function of these V-alpha12+/GD8+
T cells in order to understand their role in RA. The functions of the
cells will be examined by cytokine analyses, and in vitro functional
assays for help or inhibition of B and T cell responses. Their abundance
in RCA peripheral blood (an average of 29-30% of all CD8+ T cells)
suggests the potential for important functional effects in vivo either as
regulatory or cytotoxic T cells. It is hypothesized that these may be
autoreactive T cells that are restricted to DQ2 molecules or reactive to
DQ2 peptides. The MHC restriction and peptide specificity of the V-
alpha12+/CD8+ T cells will be characterized. These T cell clones and
receptors provide a novel tool to examine the antigens and functions that
may be of importance in this autoimmune disease.

## Key facts

- **NIH application ID:** 3159733
- **Project number:** 2R01AR039582-07
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **SAM.gov UEI:** QN6MS4VN7BD1
- **Principal Investigator:** Michael B. Brenner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $216,487
- **Award type:** 2
- **Project period:** 1988-07-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159733

## Citation

> US National Institutes of Health, RePORTER application 3159733, T-CELLS AND DISEASES (2R01AR039582-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159733. Licensed CC0.

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